The prostaglandins are an important series of molecules that have a wide variety of uses. There are many known syntheses of prostaglandins and (1S,4R) 1-acetoxy-4-hydroxycyclopent-2-ene is a known intermediate in such syntheses. (1S,4R) 1-acetoxy-4-hydroxycyclopent-2-ene has been prepared by a number of methods (see for example: Miura, S., et al., Tetrahedron, 1976, 32, 1893; Curran, T. T., et al., Tetrahedron, 1997, 53, 1983) including the enzymatic transesterification of 1,4-dihydroxycyclopent-2-ene using acetic acid esters and porcine pancreatic lipase or crude pancreatic extracts called pancreatin (Theil, F., et al., Tetrahedron, 1991, 47, 7569) to yield the 3S,5R monoacetate. The acetylations have generally been done with 2,2,2-trichloroethyl acetate as the acetylating agent and pancreatin as the enzyme. (Thiel, F., et al., Synthesis, 1988, 540-541; Thiel, F., et al. Tetrahedron, 1991, 47, 7569, 1991 and 47, 7569-7582). Subsequent procedures compared 2,2,2-trichloroethyl acetate with vinyl acetate and vinyl butyrate and also demonstrated the benefits of running the reactions in THF as the solvent with triethylamine as an additive to improve the selectivity. (Thiel, F., et al., Liebigs Ann. Chem., 1991, 195-200). However, lot-to-lot variation of enzyme catalysts lead to variable results, produce significant amounts of diacetate, and the desired monoacetate has been reported to be isolated only by costly chromatography.
Accordingly, there is a need for a process for the production of (1S,4R) 1-acetoxy-4-hydroxycyclopent-2-ene which is consistent, provides enantiomerically enriched product of enantiomeric excess of >94%, produces a minimum amount of diacetate, consumes a minimum amount of vinyl acetate and allows isolation of the product by crystallization.